Association of gene variants in the TGF-beta signalling pathways with invasive breast cancer risk

Excerpt

Many studies of normal cells in vitro, of transgenic mouse models and of somatic mutations in human cancers have provided evidence that the cytokine transforming growth factor beta (TGFβ) acts as a suppressor of primary tumour initiation. However, studies of transformed cells in vitro and of mouse models have also implicated TGFβ as a promoter of the later stages of tumour development. A hypothesis that has been proposed to account for this dual action is that TGFβ acts as a tumour suppressor through the ubiquitous ALK5 receptor signalling via SMAD2 and SMAD3 to inhibit proliferation of primary tumour cells, but acts subsequently through the endothelial-specific ALK1 receptor via SMAD1 and SMAD5 to promote angiogenesis, which is required for tumour progression [1]. …